Stimulation of abdominal visceral afferents by ischemia or skeletal muscle afferent by muscle contraction evoke strong reflex autonomic responses. Studies in our laboratory over the last 9 years have been directed at elucidating mechanisms underlying stimulation of these sensory nerve endings. We propose to extend these observations by continuing our studies of kinins, prostaglandins, PO2 and pH. Additional protocols are planned to determine if leukotrienes, serotonin, histamine and vasoactive intestinal polypeptide are involved in initiating these reflex responses or sensitizing afferent nerves during visceral ischemia or muscle contraction. Single unit afferent recordings of the T4-T8 white rami for abdominal visceral or L7-S1 for triceps surae muscle or whole animal cardiovascular reflex studies will be conducted in anesthetized cats. Abdominal visceral afferents responding to brief periods of ischemia (5-6 min) or somatic afferents responding to either static or dynamic (rhythmic) contraction will be identified and studied. Experiments are planned to measure the production of putative metabolic and mechanical factors during ischemia and muscle contraction. Venous, tissue, and lymphatic concentrations of each chemical metabolite will be assessed. Tissue concentrations will be measured from biopsy material or, in the case of PO2 and pH, with minielectrodes. Subsequently, the importance of each metabolic factor will be examined by observing the response of the afferent or reflex to exogenous administration and either specific receptor or synthesis blockade. The tension-time index will be used to compare static and dynamic muscle contraction, to study chemical and mechanical mechanisms responsible for the observed differences in afferent and reflex responses. These studies will provide new information on mechanisms of activation of visceral and somatic afferents during ischemia and muscle contraction. Comparisons between these two sensory systems will be made. Because mesenteric ischemia and exercise are associated with profound reflex cardiovascular alterations, knowledge of mechanisms underlying afferent activation will provide physicians with the possibility of modifying the untoward reactions of patients with atherosclerotic heart disease, hypertension and heart failure.